Unsaturated peroxy free radicals and cyclic peroxides of unsaturated fatty acids have been suggested as key intermediaries in lipid peroxidation due to air pollution and ionizing radiation and in prostaglandin hormone biosynthesis. The chemistry of these suggested intermediaries is not known. Because of the potential biological importance of these compounds to the regulation of vascular smooth muscles and air pollution effects on the lung, we propose to study the chemistry of unsaturated peroxy radicals with particular emphasis on: (1) Peroxy radical cyclization, (2) The activity of cyclic peroxides in smooth muscle bioassay methods for prostaglandins and (3) The suitability of these cyclic peroxides as intermediaries in lipid peroxidation. Central to the proposed synthetic approach is the development in our laboratories of a controlled method for generating specific unsaturated peroxy free radicals from hydroperoxides and cyclization of the resultant unsaturated peroxy radicals to cyclic peroxides. These methods make available a wide variety of cyclic peroxides analogous to proposed biological intermediaries. These peroxides can be studied for their biological activity, reactivity as substrates for enzymes such as prostaglandin endoperoxide isomerase, and confirmation of chemical mechanisms for the lipid peroxidation and prostaglandin biosynthesis. The results of these studies will provide a molecular framework for studies of the interaction of vascular smooth muscle with air pollutants and the chemical reactions leading to prostaglandin hormone biosynthesis.